Small-fibre neuropathy in leprosy the role of in vivo confocal microscopy: A cross-sectional study

Background: Leprosy (or Hansen’s disease) continues to present considerable challenges regarding containment and early diagnosis. Leprosy is considered to be primarily a neural disease that first affects the sensory function of small fibres. Although the condition is well described in terms of clinical manifestations and histology, few studies have been undertaken to detect damage done to small-fibre sensory nerves. In vivo confocal microscopy is a useful tool for conducting a detailed evaluation of these structures, although its use in individuals affected by leprosy has still not been explored. Objective: To evaluate in vivo confocal microscopy findings in Hansen’s disease patients and their association with clinical variables relating to this disease. Method: A cross-sectional case-series type study was carried out between October 2019 and May 2021, in Recife, Pernambuco, Brazil. Socio-demographic and clinical data were gathered from 21 patients with leprosy. The douleur neuropathique 4 neuropathic pain questionnaire was used to evaluate pain. In vivo confocal microscopy of the cornea was employed to evaluate the small-calibre fibres. Findings were compared with those for a control group of 23 healthy individuals. Results: In relation to clinical parameters, 90.5% of the patients were classified as “multibacillary” according to the World Health Organization criteria, and 70% as dimorphic or borderline, in accordance with the Madrid classification. Around 52.4% had received a diagnosis after one year or less of living with the disease, while 95.2% presented alterations in small-fibre sensory function and 35% presented such alterations in the large fibre. Neuropathic pain was present in 81% of the patients. In vivo confocal microscopy found no statistically significant difference in mean age and distribution according to sex between the Hansen disease patients and the control group of healthy individuals. The median-of-means for dendritic cells and volume of sub-basal nerve fibres in the control group were used to test for normality. Both eyes of all leprosy patients examined contained higher number of dendritic cells than the median value and a volume of sub-basal nerve fibres lower than the mean. These differences were statistically significant (P < 0.001 and P < 0.001, respectively). Multibacillary individuals had a median number of dendritic cells two times that of paucibacillary individuals (P = 0.035). Limitations: No association was found between the variables examined using in vivo confocal microscopy and clinical variables relating to small-fibre damage, the neuropathic pain questionnaire or alterations detected by the neurological examination. We believe, however, that Cochet-Bonnet esthesiometry of the cornea may have revealed such an association. Conclusion: In vivo confocal microscopy is a useful diagnostic tool for detecting small fibre loss in individuals affected by leprosy and may constitute a useful addition to the range of tools available to help curb the effects of neuropathy in these patients.

Definitions, phenomenology, diagnosis, and management of the disorders of laughter and crying in amyotrophic lateral sclerosis (ALS): Consensus from ALS and Motor Neuron Disease Scientific Department of the Brazilian Academy of Neurology / Definições, fenomenologia, diagnóstico e manejo das desordens do riso e do choro em esclerose lateral amiotrófica (ELA): Consenso do Departamento Científico de ELA e Doença do Neurônio Motor da Academia Brasileira de Neurologia

Abstract The spectrum of neuropsychiatric phenomena observed in amyotrophic lateral sclerosis (ALS) is wide and not fully understood. Disorders of laughter and crying stand among the most common manifestations. The aim of this study is to report the results of an educational consensus organized by the Brazilian Academy of Neurology to evaluate the definitions, phenomenology, diagnosis, and management of the disorders of laughter and crying in ALS patients. Twelve members of the Brazilian Academy of Neurology - considered to be experts in the field - were recruited to answer 12 questions about the subject. After exchanging revisions, a first draft was prepared. A face-to-face meeting was held in Fortaleza, Brazil on 9.23.22 to discuss it. The revised version was subsequently emailed to all members of the ALS Scientific Department from the Brazilian Academy of Neurology and the final revised version submitted for publication. The prevalence of pseudobulbar affect/pathological laughter and crying (PBA/PLC) in ALS patients from 15 combined studies and 3906 patients was 27.4% (N = 1070), ranging from 11.4% to 71%. Bulbar onset is a risk factor but there are limited studies evaluating the differences in prevalence among the different motor neuron diseases subtypes, including patients with and without frontotemporal dementia. Antidepressants and a combination of dextromethorphan and quinidine (not available in Brazil) are possible therapeutic options. This group of panelists acknowledge the multiple gaps in the current literature and reinforces the need for further studies.

Resumo O espectro de fenômenos neuropsiquiátricos observados na ELA é amplo e não completamente entendido. Desordens do riso e do choro estão entre as manifestações mais comuns. O objetivo deste estudo é relatar os resultados de um Consenso organizado pela Academia Brasileira de Neurologia para avaliar definições, fenomenologia, diagnóstico, e manejo dos distúrbios do riso e do choro em pacientes com ELA. Doze membros da Academia Brasileira de Neurologia - considerados experts na área - foram recrutados para responder 12 questões na temática. Depois da verificação das revisões, um primeiro manuscrito foi preparado. Após, foi realizado um encontro presencial em Fortaleza, Brasil, em 23/09/2022, para discussão do conteúdo. A versão revisada foi posteriormente enviada por e-mail para todos os membros do Departamento Científico de DNM/ELA da Academia Brasileira de Neurologia e a versão final revisada foi submetida para publicação. A prevalência da síndrome pseudobulbar em pacientes com ELA em 15 estudos combinados com 3906 pacientes foi de 27,4% (n = 1070), variando entre 11,4% e 71%. Início bulbar é um fator de risco, mas há limitados estudos avaliando as diferenças em prevalência entre os diferentes subtipos de Doença do Neurônio Motor, incluindo pacientes com e sem Demência Frontotemporal. Antidepressivos e uma combinação de dextrometorfana e quinidina (indisponíveis no Brasil) são opções terapêuticas possíveis. Esse grupo de panelistas reconhece as múltiplas demandas não atendidas na literatura atual e reforça a necessidade de futuros estudos.

Neuropsychiatric symptoms in vascular dementia: Epidemiologic and clinical aspects / Sintomas neuropsiquiátricos na demência vascular: aspectos clínicos e epidemiológicos

ABSTRACT Dementia is a general term for a heterogeneous group of organic neurodegenerative diseases. Cerebrovascular causes account for 20% of cases. Objective: To describe the clinical and epidemiological features of individuals aged >60 years diagnosed with vascular dementia (VD) or mixed dementia (MxD) in a referral hospital for dementia. Methods: A descriptive, retrospective study was carried out from 2014 to 2017 involving elderly individuals (≥60 years) with VA or MxD. Patients presenting other forms of dementia or in use of medication that mimics cognitive disorders were excluded. The 12-item Neuropsychiatric Inventory was used to assess neuropsychiatric symptoms (NPS). Results: 81.1% of the patients presented NPS and only 15% had two or more symptoms. Apathy was the most frequent NPS (56.6%). There was an association between CDR score 1 or 2 and NPS (OR = 6.16, 95% CI: 1.36-27.9, p = 0.02). Conclusion: Most patients had a single symptom, predominantly apathy. There was an association between mild-to-moderate dementia and NPS.

RESUMO Demência é uma terminologia geral para um grupo heterogêneo de doenças orgânicas e neurodegenerativas. As causas cerebrovasculares são responsáveis por 20% dos casos. Objetivo: Descrever as características clínicas e epidemiológicas de indivíduos maiores de 60 anos diagnosticados com demência vascular ou mista em hospital de referência em demência. Métodos: Estudo retrospectivo descritivo de 2014 a 2017 em idosos com demência. Outras formas de demência ou uso de medicamentos que mimetizem distúrbios cognitivos foram excluídos. O inventário neuropsiquiátrico de 12 itens foi usado para avaliar os sintomas neuropsiquiátricos (SNP). Resultados: 81.1% dos pacientes apresentaram SNP, apenas 15% tiveram dois ou mais. Apatia foi o mais frequente (56,6%). Houve associação entre CDR 1 ou 2 e SNP (OR = 6.16, 95% CI: 1.36-27.9, p = 0.02). Conclusão: Geralmente há um sintoma isolado, sendo apatia o principal. Encontramos associação entre demência leve e moderada e SNP.

Caracterização da epilepsia com início após os 60 anos de idade / Characterization of epilepsy with onset after 60 years of age

Resumo Introdução: Apesar da elevada incidência, a epilepsia no idoso ainda exibe peculiaridades pouco estudadas. A apresentação clínica na maioria das vezes é atípica e os achados nos exames complementares pouco ajudam no diagnóstico. Existem poucas publicações caracterizando esse grupo de indivíduos. Objetivo: Descrever as características de pacientes com epilepsia iniciada após os 60 anos de idade. Método: Foi desenvolvido estudo descritivo de série de casos, onde foram avaliados, consecutivamente, 50 pacientes com diagnóstico de epilepsia iniciada após os 60 anos de idade, atendidos no ambulatório de epilepsia do Hospital da Restauração (Recife-PE). Resultados: Dos 50 pacientes incluídos no estudo, a idade média foi de 75,3 (±13) anos, sendo que 30 (60,0%) eram do sexo feminino e 20 (40,0%) do sexo masculino. A idade média da primeira crise foi de 72,5 (±11,5) anos. Predominaram as crises epilépticas focais (83,8%). A ocorrência de estado de mal epiléptico foi baixa nesse grupo (4,0%). A epilepsia sintomática foi a mais frequente, tendo como etiologia vascular a causa mais encontrada (43,0%). A medicação mais utilizada foi a carbamazepina, e as crises apresentaram uma boa resposta terapêutica com monoterapia em dose baixa. O eletroencefalograma apresentou resultado normal em número elevado de casos (50,0%) e a neuroimagem na maioria das vezes (83,0%) apresentou achados inespecíficos. Conclusão: A epilepsia no idoso é predominantemente focal e sintomática, apresenta baixa ocorrência de estado de mal epiléptico e boa resposta terapêutica. O eletroencefalograma e a neuroimagem, na maioria das vezes, são inespecíficos.

Abstract Introduction: Despite its high incidence, the characteristics of epilepsy in elderly patients have not yet been widely studied. The clinical presentation of the disease is mostly atypical and findings from complementary examinations provide little help with diagnosis. Few reports have characterized this group of individuals. Objective: To describe the characteristics of patients with epilepsy with onset after 60 years of age. Method: A descriptive study of a case series was designed. For this purpose, 50 patients diagnosed with epilepsy with onset after 60 years of age, treated at the outpatient epilepsy clinic of the Hospital da Restauração (Recife-PE), were consecutively assessed. Results: The 50 patients included in the study had an average age of 75.3 (±13) years, 30 (60.0%) were female and 20 (40.0%) were male. The average age at the first seizure episode was 72.5 (±11.5) years. Focal epilepsy seizures were the most predominant (83.8%). The occurrence of status epilepticus was low in this group (4.0%). Symptomatic epilepsy was the most frequent type, and most of the causes were of vascular etiology (43.0%). Carbamazepine was most commonly used for treatment, and the patients responded well to low-dose monotherapy. Electroencephalograms displayed normal results in many cases (50.0%), and neuroimaging showed nonspecific findings for most individuals (83.0%). Conclusion: Epilepsy in elderly patients is predominantly focal and symptomatic, with a low occurrence of status epilepticus and good therapeutic response. The encephalogram and neuroimaging results are frequently nonspecific.

Depression and anxiety in individuals with amyotrophic lateral sclerosis: a systematic review / Depressão e ansiedade em pessoas com esclerose lateral amiotrófica: uma revisão sistemática

Introduction Studies assessing symptoms of depression and anxiety in individuals with amyotrophic lateral sclerosis (ALS) have reported contradictory results. The objective of this systematic review is to identify the prevalence of these mood disorders in the literature. Methods We searched the PubMed, HighWire, MEDLINE, SciELO, LILACS and ScienceDirect databases. Literature was selected for review in two stages, according to eligibility criteria. The first stage involved searching databases and checking titles and abstracts. The second step consisted of reading complete articles and excluding those that did not meet the inclusion criteria. The inclusion criteria were articles written in Portuguese, English or Spanish, published in the last five years and involving people with ALS diagnosed according to the El Escorial criteria. Results The database searches returned a total of 1,135 titles and abstracts and then 1,117 of these were excluded. Eighteen articles were selected for review. The 12-item Amyotrophic Lateral Sclerosis Depression Inventory (ADI-12) was the only instrument designed specifically to assess depression in ALS, but it was only used in three studies. No instruments specifically designed for anxiety in ALS were used. A large number of studies found presence and slight increase of anxiety disorders. There was considerable large variation in the results related to depressive disorders, ranging from moderate depression to an absence of symptoms. Conclusions Patients with ALS may exhibit symptoms of depression and anxiety at different levels, but there is a need for studies using specific instruments with larger samples in order to ascertain the prevalence of symptoms in ALS and the factors associated with it.

Introdução Estudos avaliando sintomas depressivos e ansiosos em pessoas com esclerose lateral amiotrófica (ELA) têm apresentado resultados contraditórios. Esta revisão sistemática tem por objetivo identificar a prevalência desses transtornos do humor na literatura. Métodos A pesquisa foi feita nas bases de dados PubMed, HighWire, MEDLINE, SciELO, LILACS e ScienceDirect. A seleção dos estudos foi realizada em duas etapas de acordo com os critérios de elegibilidade. A primeira etapa envolveu pesquisa nas bases de dados e revisão de títulos e resumos. Na segunda etapa houve a leitura dos artigos completos e a exclusão dos que não preenchiam os critérios de inclusão. Os critérios de inclusão eram: publicação nos idiomas português, inglês ou espanhol, nos últimos 5 anos e envolvendo pessoas com ELA conforme o El Escorial. Resultados Um total de 1.135 títulos e resumos foram selecionados, mas 1.117 foram excluídos. Como resultado, 18 artigos foram incluídos na revisão. O Inventário de Depressão da Esclerose Lateral Amiotrófica com 12 itens (ADI-12) foi o único instrumento específico para avaliação da depressão na ELA utilizado, porém em apenas três estudos. Nenhum instrumento específico para ansiedade na ELA foi utilizado. Boa parte dos estudos apontaram presença e ligeiro aumento das desordens de ansiedade. Já para depressão houve grande diversidade de respostas, variando de depressão moderada à ausência de sintomas. Conclusões Pessoas com ELA podem apresentar sintomas depressivos e ansiosos em proporções diferentes, mas há a necessidade de estudos com instrumentos específicos e com amostras mais amplas para que se possa averiguar a prevalência das sintomatologias na ELA e os fatores associados a elas.

Inclusion-body myositis: a difficult diagnosis? / Miosite por corpos de inclusão: um diagnóstico difícil?

Sporadic inclusion-body myositis (IBM) is the most common myopathy in individuals over 55 years of age. However, in many cases, the diagnosis is neglected. Its main findings include progressive muscle weakness, normal or low levels of serum creatine kinase, and the absence of a response to immunosuppression. Muscle biopsy shows inflammatory reaction in association with degenerative changes of the muscle fibers. We report a typical case of IBM, in which diagnosis was possible only after three muscle biopsies. The challenges to confirm histological diagnosis and the caution to avoid repeating tests are discussed.

A miosite por corpos de inclusão (MCI) esporádica é a miopatia mais comum acima dos 55 anos de idade. No entanto, em muitos casos, o diagnóstico é negligenciado. Os principais achados incluem fraqueza muscular progressiva, níveis séricos normais ou levemente elevados de creatinoquinase (CK) e ausência de resposta à imunossupressão. A biópsia muscular evidencia reação inflamatória associada com alterações degenerativas das fibras musculares. Apresentamos um caso típico de MCI cujo diagnóstico foi obtido após a realização de uma terceira biopsia muscular. Discutimos os desafios para a confirmação do diagnóstico histológico e os cuidados que podem evitar repetições do exame.

Features to validate cerebral toxoplasmosis

Introduction Neurotoxoplasmosis (NT) sometimes manifests unusual characteristics. Methods We analyzed 85 patients with NT and AIDS according to clinical, cerebrospinal fluid, cranial magnetic resonance, and polymerase chain reaction (PCR) characteristics. Results In 8.5%, focal neurological deficits were absent and 16.4% had single cerebral lesions. Increased sensitivity of PCR for Toxoplasma gondii DNA in the central nervous system was associated with pleocytosis and presence of >4 encephalic lesions. Conclusions Patients with NT may present without focal neurological deficit and NT may occur with presence of a single cerebral lesion. Greater numbers of lesions and greater cellularity in cerebrospinal fluid improve the sensitivity of PCR to T gondii. .

Aspectos eletromiográficos preditores da evolução motora de pacientes com neuroesquistossomose / Electromyografic patterns predictive of motor evolution in neuroschistosomiasis

A neuroesquistossomose na forma mielorradicular é freqüentemente observada nos pacientes que residem no Nordeste do Brasil. Apesar disso, a evolução dos seus distúrbios neurológicos e padrões eletromiográficos são pouco estudados nesse grupo de pacientes. O objetivo deste estudo foi descrever e comparar a evolução motora com as anormalidades eletromiográficas de pacientes com neuroesquistossomose. Foram realizadas eletromiografias dos membros inferiores em 21 pacientes com diagnóstico presuntivo de radiculomielite esquistossomótica. O padrão eletromiográfico de 95,2 por cento dos casos foi de multirradiculopatia axonal lombo-sacra, havendo extensão variável de desnervação, com predomínio de L2 a S2. Foram identificados graus variáveis de paraparesia, havendo evolução motora mais favorável nos pacientes com envolvimento de menor número de raízes. A eletromiografia poderá fornecer dados prognósticos da evolução motora dos pacientes com radiculomielite esquistossomótica.

Neuroschistosomiasis in myeloradicular pattern is frequently observed in patients from Northeast of Brazil. Despite of this, the evolution of neurologic and electromyografic patterns is not well studied in this group of patients. The aims of this study were to describe and compare the clinic and electromyografic abnormalities of patients with neuroschistosomiasis and radicular involvement. We analyzed 21 electromyographic exams of the lower limbs carried out in the initial presentation of the disease. Electromyographic pattern of 95.2 percent of patients was compatible to axonal lombosacral multirradiculopathy, with variable denervation extension, but predominanthy from levels L2 to S2. There was variable degree of deficit in the lower limbs, and the follow-up of motor disturbances was better more frequently when the roots were involved in smaller number. Electromyography should permit to know the motor prognosis of patients with myeloradiculitis due schistosomiasis.